Norethindrone Tablets
» Norethindrone Tablets contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of norethindrone C20H26O2.
Packaging and storage— Preserve in well-closed containers.
Labeling— When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used.
Identification— Mix a portion of powdered Tablets, equivalent to about 50 mg of norethindrone, with 15 mL of solvent hexane, and stir occasionally for 15 minutes. Centrifuge the mixture, then decant and discard the solvent hexane. Extract the residue with two 10-mL portions of solvent hexane, centrifuging and decanting as before, and discard the solvent hexane. Add 25 mL of chloroform to the residue, mix by shaking for 1 to 2 minutes, and filter. Evaporate the filtrate to about 3 mL, add a few mL of solvent hexane to induce crystallization, and evaporate to dryness: the IR absorption spectrum of a potassium bromide dispersion prepared from the residue so obtained exhibits maxima only at the same wavelengths as that of a similar preparation of USP Norethindrone RS.
Dissolution 711—
test 1—
Medium: 0.09% sodium lauryl sulfate in 0.1 N hydrochloric acid; 500 mL, deaerated.
Apparatus 2: 75 rpm.
Time: 30 minutes.
Determine the amount of C20H26O2 dissolved by employing the following method.
Mobile phase— Prepare a filtered and degassed mixture of water and acetonitrile (3:2). Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard solution— Transfer about 35 mg, accurately weighed, of USP Norethindrone RS to a 500-mL volumetric flask. Add approximately 100 mL of methanol, and sonicate until completely dissolved. Cool to room temperature. Dilute with methanol to volume, and mix well. Transfer 2.0 mL of this solution to a 200-mL volumetric flask. Dilute with Medium to volume, and mix well.
Test solution— Pass the solution under test through a suitable 0.45-µm filter.
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm × 15-cm column that contains 5-µm packing L7. The flow rate is about 1.5 mL per minute. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections is not more than 3.0%.
Procedure— Separately inject equal volumes (about 100 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the peak responses. Calculate the percentage of norethindrone dissolved by the formula:
Click to View Image
in which rU and rS are the peak responses for the Test solution and the Standard solution, respectively; CS is the concentration, in mg per mL, of norethindrone in the Standard solution; 500 is the volume, in mL, of Medium; 100 is the conversion factor to percentage; and LC is the Tablet label claim, in mg.
Tolerances— Not less than 80% (Q) of the labeled amount of C20H26O2 is dissolved in 30 minutes.
test 2— If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.
Medium: 0.09% sodium lauryl sulfate in 0.1 N hydrochloric acid; 500 mL, deaerated.
Apparatus 2: 75 rpm.
Time: 45 minutes.
Determine the amount of C20H26O2 dissolved by employing the following method.
Mobile phase— Prepare a filtered and degassed mixture of 0.02 M phosphate buffer pH 6.0 and acetonitrile (65:35). Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard solution— Transfer about 14 mg, accurately weighed, of USP Norethindrone RS to a 100-mL volumetric flask. Dilute with methanol to volume, and mix. Transfer 20.0 mL of this solution to a 100-mL volumetric flask. Dilute with methanol to volume, and mix. Transfer 5.0 mL of this solution to a 200-mL volumetric flask. Dilute with Medium to volume, and mix.
Test solution— Pass the solution under test through a suitable 0.45-µm filter, or centrifuge at least 10 mL of the solution under test and use the supernatant.
Chromatographic system (see Chromatography 621)— Use one of the following two chromatographic systems:
Chromatographic system 1— The liquid chromatograph is equipped with a 200-nm detector and a 4.6-mm × 10-cm column that contains 3-µm packing L1. The flow rate is about 1.0 mL per minute.
Chromatographic system 2— The liquid chromatograph is equipped with a 240-nm detector and a 4.6-mm × 10-cm column that contains 3- or 3.5-µm packing L1. The flow rate is about 2.0 mL per minute.
Using either Chromatographic system 1 or 2, chromatograph the Standard solution, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections is not more than 3.0%.
Procedure— Proceed as directed for Test 1. Calculate the percentage of norethindrone dissolved by the formula:
Click to View Image
in which rU and rS are the peak responses for the Test solution and the Standard solution, respectively; CS is the concentration, in mg per mL, of norethindrone in the Standard solution; 500 is the volume, in mL, of Medium; 100 is the conversion factor to percentage; and LC is the Tablet label claim, in mg.
Tolerances— Not less than 80% (Q) of the labeled amount of C20H26O2 is dissolved in 45 minutes.
Uniformity of dosage units 905: meet the requirements.
Assay—
Isoniazid reagent— Dissolve 1.0 g of isoniazid in 1000 mL of anhydrous methanol, add 1.3 mL of hydrochloric acid, and mix.
Procedure— Weigh and finely powder not less than 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 0.7 mg of norethindrone, to a 50-mL volumetric flask, and add anhydrous methanol to volume. Mix, and allow to stand for 10 minutes, with occasional mixing. Filter a portion of the mixture to clarify the solution, and transfer 10.0 mL of the filtrate to a suitable container. Add 2.0 mL of Isoniazid reagent, mix, seal, and allow to stand for 30 minutes. This is the Assay preparation. Transfer a second 10.0-mL portion of the filtrate to a suitable container, add 2.0 mL of methanol, and mix. This is the Assay blank preparation. Transfer 10.0 mL of methanol to a suitable container, add 2.0 mL of Isoniazid reagent, mix, seal, and allow to stand for 30 minutes. This is the Reagent blank preparation. Prepare a Standard preparation by transferring 10.0 mL of a solution of USP Norethindrone RS in methanol having a concentration of about 14 µg per mL to a suitable container. Add 2.0 mL of Isoniazid reagent, mix, seal, and allow to stand for 30 minutes. Concomitantly determine the absorbances of these solutions in 1-cm cells, at about 380 nm, with a suitable spectrophotometer, using methanol as the reference for the Assay blank preparation, and using the Reagent blank preparation as the reference for the Assay preparation and the Standard preparation. Calculate the quantity, in mg, of C20H26O2 in the portion of Tablets taken by the formula:
0.05C(AU AB) / AS
in which C is the concentration, in µg per mL, of the Standard preparation, and AU, AB, and AS are the absorbances of the Assay preparation, the Assay blank preparation, and the Standard preparation, respectively.
Auxiliary Information— Please check for your question in the FAQs before contacting USP.
Topic/Question Contact Expert Committee
Monograph Daniel K. Bempong, Ph.D.
Senior Scientist
1-301-816-8143		 (MDPS05) Monograph Development-Pulmonary and Steroids
Reference Standards Lili Wang, Technical Services Scientist
1-301-816-8129
RSTech@usp.org
711 Margareth R.C. Marques, Ph.D.
Senior Scientist
1-301-816-8106		 (BPC05) Biopharmaceutics05
USP32–NF27 Page 3105
Pharmacopeial Forum: Volume No. 33(6) Page 1193
Chromatographic Column—
Chromatographic columns text is not derived from, and not part of, USP 32 or NF 27.